Autologous IC-Nine, CD30 CAR, and Constitutive IL7R Expressing EBVST for CD30 Lymphoma (ANCILE-30) (ANCILE-30)
This Phase I study will evaluate the safety of autologous Epstein-Barr virus-specific T lymphocytes modified to express a constitutively active IL7 receptor (C7R) and a chimeric antigen receptor (CAR) for CD30 (C7R.CD30-CAR-EBVSTs) in patients with relapsed or refractory CD30-positive lymphomas.
Participants who meet procurement eligibility criteria will undergo collection of peripheral blood mononuclear cells for manufacture of the investigational product. Participants with a successfully manufactured product who continue to meet treatment eligibility criteria will receive lymphodepleting chemotherapy followed by infusion of autologous C7R.CD30-CAR-EBVSTs.
The primary objective is to evaluate safety. Secondary and exploratory objectives include evaluation of antitumor effect, expansion and persistence of the infused cells, and the association between immunological parameters, safety, and clinical response.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
This is a Phase I study to evaluate the safety of autologous Epstein-Barr virus-specific T lymphocytes (EBVSTs) genetically modified to express a constitutively active interleukin-7 receptor (C7R) and a CD30-specific chimeric antigen receptor (CAR) (C7R.CD30-CAR-EBVSTs) in patients with relapsed or refractory CD30-positive lymphomas. The study will also evaluate the antitumor effect of C7R.CD30-CAR-EBVSTs, the expansion and persistence of the infused cells, and the association between immunological parameters, safety, and clinical response.
Autologous CD30 CAR T cells have demonstrated clinical activity in patients with relapsed or refractory CD30-positive lymphomas but have shown limited persistence. Epstein-Barr virus-specific T lymphocytes (EBVSTs) have demonstrated long-term persistence following adoptive transfer. In this study, EBVSTs are used as the cellular platform to express both a CD30 CAR and a constitutively active IL7 receptor (C7R). The investigational cell product also provides a mechanism for rapid elimination of transduced cells if clinically indicated.
Participants who meet procurement eligibility criteria will undergo collection of peripheral blood mononuclear cells for manufacture of an autologous C7R.CD30-CAR-EBVST product. Participants with a successfully manufactured product who continue to meet treatment eligibility criteria will receive lymphodepleting chemotherapy followed by intravenous infusion of C7R.CD30-CAR-EBVSTs. Participants who meet retreatment criteria, as defined in the protocol, may receive additional treatment cycles. Following treatment, participants will undergo scheduled follow-up evaluations including physical examinations, laboratory testing, and imaging studies to assess safety and disease status.
Blood samples are collected at multiple time points after infusion to evaluate persistence of the infused cells. Tumor assessments are performed using imaging and, when clinically indicated, biopsy.
Participants are followed longitudinally for up to 15 years after the most recent infusion.
Tipo de estudo
Inscrição (Estimado)
Estágio
- Fase 1
Contactos e Locais
Contato de estudo
- Nome: Premal Lulla, MD
- Número de telefone: 713-441-1450
- E-mail: lulla@bcm.edu
Locais de estudo
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Texas
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Houston, Texas, Estados Unidos, 77030
- Houston Methodist Hospital
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Contato:
- Premal Lulla, MD
- Número de telefone: 713-441-1450
- E-mail: lulla@bcm.edu
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
- Filho
- Adulto
- Adulto mais velho
Aceita Voluntários Saudáveis
Descrição
Procurement Inclusion Criteria:
Participants must meet the protocol-defined procurement eligibility criteria before collection of peripheral blood mononuclear cells for manufacture of the investigational product, including:
- Diagnosis of relapsed or refractory Hodgkin lymphoma or non-Hodgkin lymphoma.
- CD30 positive tumor (can be pending at this time) as assayed in a CLIA certified Pathology Laboratory.
- Age 16 to 75 years.
- Hemoglobin ≥7.0(may be transfused value).
- Karnofsky or Lansky score of > 60%
- Informed consent explained to, understood by and signed by patient or guardian. Patient or guardian given copy of informed consent.
Procurement Exclusion Criteria:
- Active HIV or HTLV infection (testing may be pending at procurement).
Active bacterial, fungal, or viral infection.
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Treatment Inclusion Criteria:
Participants with a successfully manufactured product must continue to satisfy the protocol-defined treatment eligibility criteria before receiving study treatment, including:
Diagnosis and clinical course falling into one of the following categories:
- Hodgkin lymphoma
- CD30+ aggressive B-cell lymphoma
- ALK-negative anaplastic T cell lymphoma or other peripheral T- cell lymphoma
- ALK-positive anaplastic T cell lymphoma
- CD30 expression confirmed in a CLIA-certified laboratory. Recovered from all acute non-hematologic toxic effects of all prior chemotherapy
- Age 16 to 75 years.
- Bilirubin ≤ 2 times the upper limit of normal (except for Gilbert syndrome, where the criteria will be Bilirubin ≤ 3 times the upper limit of normal).
- AST ˂ 3 times the upper limit of normal
- Estimated GFR > 50 mL/min
- Pulse oximetry of > 90% on room air
- Karnofsky or Lansky score of > 60%
- Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 6 months after study is concluded. Male partner should use a condom
- Informed consent explained to, understood by and signed by patient/guardian. Patient/Guardian given copy of informed consent.
Treatment Exclusion Criteria:
- Received an investigational cell therapy or vaccine within the past 6 weeks.
- Received an investigational small molecule within the past 2 weeks.
- Received anti-CD30 antibody-based therapy within the previous 4 weeks.
- History of hypersensitivity reactions to murine protein-containing products
- Pregnancy or breastfeeding.
- Tumor in a location where enlargement could cause airway obstruction (determined at the investigators' discretion)
- Current use of systemic corticosteroids at a dose equivalent to higher than 10 mg/day of prednisone.
- Active significant, uncontrolled bacterial, viral or fungal infection.
- Symptomatic cardiac disease (NYHA Class III or IV disease).
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: N / D
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Experimental: Autologous C7R.CD30-CAR-EBVSTs
Participants who meet procurement eligibility criteria will undergo collection of peripheral blood mononuclear cells for manufacture of autologous C7R.CD30-CAR-EBVSTs.
Participants with a successfully manufactured product who continue to meet treatment eligibility criteria will receive lymphodepleting chemotherapy followed by intravenous infusion of autologous C7R.CD30-CAR-EBVSTs.
Participants who meet protocol-defined retreatment criteria may receive additional treatment cycles.
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Autologous Epstein-Barr virus-specific T lymphocytes genetically modified to express a constitutively active interleukin-7 receptor (C7R), a CD30-specific chimeric antigen receptor (CAR), and an inducible caspase 9 (iC9) safety switch.
The investigational product is manufactured from autologous peripheral blood mononuclear cells and administered by intravenous infusion following lymphodepleting chemotherapy.
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Incidence of Dose-Limiting Toxicities (DLTs)
Prazo: From initiation of lymphodepleting chemotherapy through 28 days following the initial investigational T-cell infusion.
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Dose-limiting toxicity (DLT) is defined as any of the following considered possibly, probably, or definitely related to study cellular products: (1) Grade 5 event without disease progression; (2) CRS: Grade 4, or Grade 3 not improving to ≤Grade 2 within 72 hours despite therapy; (3) ICANS: Grade 4, or Grade 3 not improving within 72 hours despite therapy; (4) Grade ≥3 IEC-HS; (5) Grade 4 neutropenia or thrombocytopenia not attributable to underlying disease or lymphodepleting chemotherapy and not improving to ≤Grade 2 within 42 days, or Grade 3 thrombocytopenia with clinically significant major bleeding; (6) Grade ≥3 vital organ toxicity (except transient hepatic or renal abnormalities improving to ≤Grade 2 within 7 days); (7) other Grade 3 toxicities not attributable to underlying disease or lymphodepleting chemotherapy and not resolving to ≤Grade 2 within 72 hours; (8) Grade ≥2 allergic reaction to T-cell infusion.
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From initiation of lymphodepleting chemotherapy through 28 days following the initial investigational T-cell infusion.
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Antitumor Effect
Prazo: 4 to 6 weeks after the initial C7R.CD30-CAR-EBVST infusion.
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Antitumor effect will be assessed by investigator evaluation of objective response (complete response and partial response) using Lugano criteria.[
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4 to 6 weeks after the initial C7R.CD30-CAR-EBVST infusion.
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Helen Heslop, MD, The Methodist Hospital Research Institute
- Investigador principal: Premal Lulla, MD, The Methodist Hospital Research Institute
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Estimado)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Neoplasias
- Doenças do sistema imunológico
- Neoplasias por Tipo Histológico
- Doenças Linfáticas
- Distúrbios Linfoproliferativos
- Distúrbios imunoproliferativos
- Linfoma Não-Hodgkin
- Linfoma de Células B
- Linfoma
- Linfoma de Células T
- Doenças hemic e linfáticas
- Linfoma de Células B Grandes Difuso
- Doença de Hodgkin
- Linfoma de Células T Periférico
- Linfoma de Células Grandes Anaplásico
Outros números de identificação do estudo
- ANCILE-30
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
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